High grade astrocytomas represent the most common brain malignancies with limited therapeutic options available and proven association with generally poor clinical outcomes. Improved understanding of disease etiology thus represents a promising avenue for developing innovative diagnostic and therapeutic strategies. The project encompases a broad set of collaborative efforts among CAPR, Dr. Van Dyke's previous laboratory, and Dr. Leroy Hood's lab at the ISB to characterize molecular signatures and pathways underlying the astrocytomagenesis process and to identify promising early prognostic markers of cancerous transformation as well as response to therapeutic treatment. To this end, the project leverages the advantages of inducible disease initiation in the mouse, the ability to perturb and/or monitor the carcinogenesis process, and the extensive power of unbiased systems biology approach. The computational analysis of transcriptome changes with time and disease stage has been completed and reveals numerous networks that distinctively change as tumors progress. Initiation of disease is associated with networks involved in cell cycle activity, stem cell signatures, and glioma properties. As disease progresses, networks associated with inflammatory processes and cell-cell interaction and invasion dominate. A manuscript describing these results is in preparation. The study to utilize the intracranial transplant model in the development of ultrasound methodology to improve brain and tumor permeability for therapeutics is still in progress.